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Vitamin C and cancer
Most of my current research revolves around determining the biological functions of vitamin C (ascorbate), which is widely considered to be an important natural antioxidant. However, ascorbate is also an essential co-factor for a family of enzymes, the 2-oxoglutarate-dependent dioxygenases, which control many biological processes, ranging from the stress response to hypoxia, to the regulation of epigenetic enzymes. These processes are important in cancer and we are investigating the contribution of ascorbate to cancer growth as a result of its co-factor activity for these enzymes. We are planning clinical trials to determine the impact of ascorbate on the processes involved in cancer cell biology.
Vitamin C and immunity
The cofactor activities of ascorbate are likely to influence many biological processes that impact on health and disease, and our aim is to understand the extent of this involvement in the functioning of the immune system. My research has shown that ascorbate affects white blood cell function, and we have an interest in the role of ascorbate in acute inflammatory diseases such as pneumonia and sepsis.
Vitamin C and optimal health
We have investigated the comparative bioavailability of vitamin C from different sources (i.e. food-derived or synthetic) to organs and tissues in an animal model and human subjects. This research will help to inform the debate around the appropriate Nutrient Reference Value and Recommended Dietary Intake for vitamin C. Ascorbate acts as a cofactor for the enzymatic synthesis of mood and energy controlling hormones. We have investigated the association of vitamin C intake from an excellent food source (kiwifruit) with measures of subjective mood, including fatigue, and shown that a high vitamin C diet can improve mood and energy levels. This preliminary research will be followed up with a larger clinical study.
White blood cells and inflammation
My research interests also include the investigation of cellular responses to stress, in particular stress resulting from exposure to oxidants. I have extensive experience in working with inflammatory cells, particularly neutrophils, as a source of highly reactive oxidants. Neutrophils generate hypochlorous acid (HOCl), i.e. household bleach, which is known for its anti-microbial activity. HOCl also reacts with many biological targets, as we are investigating how it damages cells and tissues, and how it contributes to the many deleterious effects of chronic inflammatory diseases such as atherosclerosis. The oxidative stress-related processes we are most interested in are apoptosis (cell clearance from sites of inflammation), cell signalling (e.g. nuclear factor-kB; NFkB, and hypoxia-inducible factor 1a; HIF-1) and cytotoxicity (cell death).
Keywords: cancer, immunity, vitamin C (ascorbate), inflammation, atherosclerosis, oxidative stress, antioxidants.
In the media
Professor Margreet Vissers was featured in Radio New Zealand's The Science Of... Vitamin C in August 2017.
Praditi, C., Bozonet, S. M., Dachs, G. U., & Vissers, M. C. M. (2023). Ascorbate uptake and retention by breast cancer cell lines and the intracellular distribution of sodium-dependent vitamin C transporter 2. Antioxidants, 12, 1929. doi: 10.3390/antiox12111929
Coker, S. J., Dyson, R. M., Smith-Díaz, C. C., Vissers, M. C. M., & Berry, M. J. (2023). Effects of low vitamin C intake on fertility parameters and pregnancy outcomes in guinea pigs. Nutrients, 15, 4107. doi: 10.3390/nu15194107
Peeters, W. M., Gram, M., Dias, G. J., Vissers, M. C. M., Hampton, M. B., Dickerhof, N., Bekhit, A. E., … Bayer, S., … Sheard, P. W., Danielson, K. M., … Cornwall, J., & Rowlands, D. S. (2023). Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes. Redox Biology, 67, 102918. doi: 10.1016/j.redox.2023.102918
Bozonet, S. M., Magon, N. J., Schwartfeger, A. J., Konigstorfer, A., Heath, S. G., Vissers, M. C. M., … Göbl, C., … Hampton, M. B. (2023). Oxidation of caspase-8 by hypothiocyanous acid enables TNF-mediated necroptosis. Journal of Biological Chemistry, 104792. Advance online publication. doi: 10.1016/j.jbc.2023.104792
Vissers, M., Smith-Díaz, C., Coker, S., Dyson, R., Hore, T., & Berry, M. (2022, August-September). Low maternal vitamin C during pregnancy in guinea pigs results in persistent epigenetic dysregulation in the hippocampus of offspring together with an ADHD-related phenotype. Poster session presented at the 31st Queenstown Molecular Biology Meeting (QMB), Queenstown, New Zealand.